Activation of Ca sup 2+ uptake and inhibition of reversal of the sarcoplasmic reticulum Ca sup 2+ pump by aromatic compounds

Journal Article · Tue Dec 05 00:00:00 EST 1989 · Journal of Biological Chemistry; (USA)

OSTI ID:5025798

Petretski, J H; Wolosker, H; de Meis, L ^[1]

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1. Universidade Federal do Rio de Janeiro (Brazil)

The effects of aromatic compounds in sarcoplasmic reticulum Ca2+-ATPase were investigated. The solubility of the drugs in various organic solvents and water was measured. The ratio between the solubility in organic solvents and that in water (distribution coefficient) was used as an index of their hydrophobicity. The order found was triphenylphosphine greater than diphenylamine greater than 3-nitrophenol greater than 4-nitrophenol greater than 1,3-dihydroxybenzene. The effects observed on the Ca2+-ATPase were correlated with hydrophobicity of the drugs, activation and inhibition being obtained at a lower concentration the greater the distribution coefficient of the drug into organic solvent. In leaky vesicles, the effects of each compound on the ATPase activity varied depending on the Ca2+ concentration in the medium: it inhibited in the presence of 5 microM Ca2+ and activated when the Ca2+ concentration was raised to 2 mM. In intact vesicles, 3- and 4-nitrophenol, diphenylamine, and triphenylphosphine enhanced both the rate of ATP hydrolysis and the amount of Ca2+ accumulated by the vesicles. These four drugs inhibited Ca2+ uptake when ITP was used as substrate. 1,3-Dihydroxybenzene enhanced the amount of Ca2+ accumulated by the vesicles regardless of whether ATP or ITP was the substrate. All five compounds inhibited the phosphorylation of the enzyme by Pi, the efflux of Ca2+, and the synthesis of ATP measured during the reversal of the Ca2+ pump. The results indicate that the hydrophobic character of various organic compounds determines their access to sensitive domains of the membrane-bound calcium pump. Additional specific effects are then produced, depending on the structure of each compound.

• OSTI ID: 5025798
• Journal Information: Journal of Biological Chemistry; (USA), Vol. 264:34; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
CALCIUM COMPOUNDS
MEMBRANE TRANSPORT
NITROPHENOL
METABOLISM
ORGANIC SOLVENTS
ATP-ASE
CELL MEMBRANES
MUSCLES
PHOSPHATES
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
RABBITS
SARCOPLASMIC RETICULUM
TRACER TECHNIQUES
WATER
ACID ANHYDRASES
ALKALINE EARTH METAL COMPOUNDS
ANIMALS
AROMATICS
CELL CONSTITUENTS
CHEMICAL REACTIONS
ENDOPLASMIC RETICULUM
ENZYMES
HYDROGEN COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MEMBRANES
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
OXYGEN COMPOUNDS
PHENOLS
PHOSPHOHYDROLASES
PHOSPHORUS COMPOUNDS
SOLVENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques